Discipline: Biological Sciences
Subcategory: Cancer Research
Charmonix Williams - Jackson State University
Brain Tumors (Glioblastomas) have tormented society for generations and eluded treatment and strike fear in those affected. Neoplasms or tumors are abnormal masses of tissue that result when cells divide more than they should. Glioblastomas arise from astrocytes, star shaped supportive tissue of the brain. They are found in the brain and spinal cord. Therapeutic agents targeting glioblastomas have proven to be highly ineffective in clinical settings and disappointing hence, survival is only extended from 2 months to 1 year. This poor prognosis has led to focus on identifying novel molecular targets against glioblastoma and the signaling mechanism through which they act. While many targets are variably expressed in glioblastomas cell lines, the challenge has been to identify those that engage the downstream signaling components in a functional relevant manner, FOXO3a, a member of the forkhead transcription factor family, acts as a tumor suppressor. FOXO3a has been shown to be a critical regulator of the expression of several apoptotic factors such as TNF-Related Apoptosis Inducing Ligand (TRAIL). The functional role of FOXO3a in glioblastomas has not been investigated. To combat this deadly tumor type, we use a genetic approach of over expressing transcriptional factor FOXO3a. We hypothesize that over expression of FOXO3a provides resistance to oxidative stress, halts cell cycle progression, and controls the induction of cellular death in glioblastoma cells, U87. These studies provide novel insight into the mechanism by which FOXO3a modulates cell transformation and generates effective anti-cancer therapies. In the preliminary experiment, we grew four glioblastoma cell types (U-87, LN-18, LN-229, LN-319). After harvest we identified which of the glioblastoma types displayed Foxo3a expression. Images 5 and 6 show the result of the western blots used to determine the levels of Foxo3a endogenous protein expression in various glioblastoma cell lines. Cells that expressed low levels of Foxo3a will be transfected with Foxo3a construct. Cells undergoing apoptosis will be assessed using FACS analysis. When over expressed in U-87 glioblastoma cells it induces apoptosis. This result was confirmed using cytometeric analysis.
Funder Acknowledgement(s): LSAMP; MARC
Faculty Advisor: Kenneth Ndebele Duma, Kenduma@yahoo.com
Role: I did everything. My ideas are shared with my mentor's interest. I carried out all experiments.